Transcription factor FOXO3a controls the persistence of memory CD4 + T cells during HIV infection

Julien Van Grevenynghe, Francesco A. Procopio, Zhong He, Nicolas Chomont, Catherine Riou, Yuwei Zhang, Sylvain Gimmig, Genevieve Boucher, Peter Wilkinson, Yu Shi, Bader Yassine-Diab, Elias A. Said, Lydie Trautmann, Mohamed El Far, Robert S. Balderas, Mohamed Rachid Boulassel, Jean Pierre Routy, Elias K. Haddad, Rafick Pierre Sekaly

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121 Citations (Scopus)

Abstract

The persistence of central memory CD4+ T cells (TCM cells) is a major correlate of immunological protection in HIV/AIDS, as the rate of TCM cell decline predicts HIV disease progression. In this study, we show that TCM cells and effector memory CD4+ T cells (TEM cells) from HIV+ elite controller (EC) subjects are less susceptible to Fas-mediated apoptosis and persist longer after multiple rounds of T cell receptor triggering when compared to TCM and T EM cells from aviremic successfully treated (ST) subjects or from HIV- donors. We show that persistence of TCM cells from EC subjects is a direct consequence of inactivation of the FOXO3a pathway. Silencing the transcriptionally active form of FOXO3a by small interfering RNA or by introducing a FOXO3a dominant-negative form (FOXO3a Nt) extended the long-term survival of TCM cells from ST subjects to a length of time similar to that of TCM cells from EC subjects. The crucial role of FOXO3a in the survival of memory cells will help shed light on the underlying immunological mechanisms that control viral replication in EC subjects.

Original languageEnglish
Pages (from-to)266-274
Number of pages9
JournalNature Medicine
Volume14
Issue number3
DOIs
Publication statusPublished - Mar 2008

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Van Grevenynghe, J., Procopio, F. A., He, Z., Chomont, N., Riou, C., Zhang, Y., Gimmig, S., Boucher, G., Wilkinson, P., Shi, Y., Yassine-Diab, B., Said, E. A., Trautmann, L., Far, M. E., Balderas, R. S., Boulassel, M. R., Routy, J. P., Haddad, E. K., & Sekaly, R. P. (2008). Transcription factor FOXO3a controls the persistence of memory CD4 + T cells during HIV infection. Nature Medicine, 14(3), 266-274. https://doi.org/10.1038/nm1728